crossing96/oncoscreening huggingface dataset:
ELK1 is up-regulated by androgen in bladder cancer cells and promotes tumor progression.	Little is known about biological significance of ELK1, a transcriptional factor that activates downstream targets including c-fos proto-oncogene, in bladder cancer. Recent preclinical evidence also suggests the involvement of androgen receptor (AR) signaling in bladder cancer progression. In this study, we aim to investigate the functions of ELK1 in bladder cancer growth and their regulation by AR signals. Immunohistochemistry in bladder tumor specimens showed that the levels of phospho-ELK1 (p-ELK1) expression were significantly elevated in urothelial neoplasms, compared with non-neoplastic urothelium tissues, and were also correlated with AR positivity. Patients with p-ELK1-positive non-muscle-invasive and muscle-invasive tumors had significantly higher risks for tumor recurrence and progression, respectively. In AR-positive bladder cancer cell lines, dihydrotestosterone treatment increased ELK1 expression (mRNA, protein) and its nuclear translocation, ELK1 transcriptional activity, and c-fos expression, which was restored by an anti-androgen hydroxyflutamide. ELK1 silencing via short hairpin RNA (shRNA) resulted in decreases in cell viability/colony formation, and cell migration/invasion as well as an increase in apoptosis. Importantly, ELK1 appears to require activated AR to regulate bladder cancer cell proliferation, but not cell migration. Androgen also failed to significantly induce AR transactivation in ELK1-knockdown cells. In accordance with our in vitro findings, ELK1-shRNA expression considerably retarded tumor formation as well as its growth in xenograft-bearing male mice. Our results suggest that ELK1 plays an important role in bladder tumorigenesis and cancer progression, which is further induced by AR activation. Accordingly, ELK1 inhibition, together with AR inactivation, has the potential of being a therapeutic approach for bladder cancer.	bladder
Comparison of structural genetics of non-schistosoma-associated squamous cell carcinoma of the urinary bladder.	Little is known about genetic changes in squamous differentiation of non-schistosomiasis-associated bladder cancer. Therefore, we investigated pure squamous cell carcinomas (SqCC), squamous parts of mixed urothelial carcinomas with squamous differentiation (MIX) and mere urothelial cancers (UC) for structural genetic differences. Tissue microarray slides (n = 29 SqCC, n = 35 MIX and n = 23 UC) were analyzed by ZytoLight SPEC p16/CEN3/7/17 Quadruple Color Probe fluorescence-in-situ-hybridization (FISH) and DNA was investigated by comparative genomic hybridization (CGH) (n = 35 SqCCs, n = 40 MIX and n = 36 UC). By FISH the mean number of polysomic cells was lowest in SqCC (CEN3 P = 0.0498, CEN17 P = 0.0009). A slight tendency of lower copy numbers of chromosomes 3, 7 and 17 and higher numbers of the p16-locus in SqCC (P = 0.45) indicated less aneuploid tumor cells in SqCC compared to MIX and UC. In CGH SqCC showed the lowest mean number of aberrations per tumor (SqCC 5.37 changes, MIX 6.75 and UC 7.64; P = 0.1754). Significant differences between the three groups were found for loss of chromosome 3p (P = 0.004), 6q (P = 0.028), 11p (P = 0.024) and gains of 5p (P = 0.020). Loss of 3p was more frequent in SqCC (51.4%) than in MIX (37.5%) or UC (13.9%). To conclude, SqCCs show less polysomy and genetic alterations than MIX and UC. Loss of 3p is more frequent in SqCC but there are no absolute specific alterations for each tumor group. Squamous parts of mixed tumors show similar alterations than UC and should be considered as further development of UC, while pure SqCC seem to be a separate tumor group.	bladder
Sarcopenia Evaluated Using the Skeletal Muscle Index Is a Significant Prognostic Factor for Metastatic Urothelial Carcinoma.	BACKGROUND: The purpose of the study was to evaluate the prognostic value of sarcopenia (muscle loss) in patients with metastatic urothelial carcinoma (UC), in a comparison of several methods of computed tomography (CT)-based evaluation of sarcopenia. PATIENTS AND METHODS: We retrospectively reviewed 100 patients with metastatic UC who underwent first-line systemic chemotherapy between 2003 and 2014. Sarcopenia was assessed by the following CT-based methods: skeletal muscle index (SMI), total psoas area (TPA), axial and/or transversal psoas thickness at the level of the third lumbar vertebrae, and axial and/or transversal psoas thickness at the umbilicus level (U-TPT). All parameters were standardized by either height or height squared. Cutoff points were SMI: < 55 cm(2)/m(2) (men), < 39 cm(2)/m(2) (women); others: lowest sex-specific quartiles. Predictive values for cancer-specific survival (CSS) were assessed using the Cox proportional hazards regression model. RESULTS: Sixty-four patients met the eligibility criterion for analysis: those who underwent CT scans within 30 days before chemotherapy. Of them, 52 (81%) died of UC during the follow-up, with a median survival time of 13 months. Univariate analysis associated decreased SMI, TPA, and U-TPT with poor CSS. Multivariate analysis together with other pretreatment clinicopathologic parameters showed decreased SMI to be an independent predictor of poor CSS. CONCLUSION: Evaluation using SMI showed sarcopenia was an independent predictor of poor prognosis for patients with metastatic UC who underwent first-line systemic chemotherapy. Our results might improve stratification of patients and help optimize evaluation of sarcopenia.	bladder
Contemporary radical cystectomy outcomes in patients with invasive bladder cancer: a population-based study.	OBJECTIVE: To determine the contemporary survival outcomes from a whole population and identify significant predictors of survival, as contemporary population-based survival outcomes after radical cystectomy (RC) for the treatment of bladder cancer (BC) are sparse. Reports suggest a large disparity between population outcomes and those of centres of excellence. PATIENTS AND METHODS: All invasive BC cases diagnosed between 2001 and 2007 in New South Wales, Australia, were identified from the Central Cancer Registry. Records of treatment and death were electronically linked. All patients who underwent RC between 2001 and 2009 were selected for this study (804 patients). Follow-up was to the end of 2009. Outcomes assessed were disease-specific survival (DSS) and overall survival (OS). Multivariable Cox regression and log-rank analysis were used to model and compare survival within groups. RESULTS: Of 804 patients diagnosed during the study period 420 (52.2%) died during follow-up. The 5-year DSS and OS for all patients was 59.6% and 53.2%, respectively. The 5-year DSS for patients with localised, regional and distant disease, undergoing RC was 72%, 51% and 10%, respectively. Age (P < 0.001) and stage (P < 0.001) were associated with 5-year DSS and OS after adjusting for all other variables. High-volume centres had significantly better 5-year DSS compared with low-volume centres (P < 0.05). The 30-day mortality for high- vs low-volume centres was 1.8% and 3.6%, respectively. Perioperative mortality improved over time for high- and moderate-volume centres but not for low-volume centres. CONCLUSION: Contemporary survival outcomes after RC are much improved compared with older studies and appear close to results from academic centres of excellence. High-volume centres report better 5-year DSS outcomes than lower volume centres.	bladder
The Utility of a Flexible Fluorescence-Cystoscope with a Twin Mode Monitor for the 5-Aminolevulinic Acid-Mediated Photodynamic Diagnosis of Bladder Cancer.	OBJECTIVES: To evaluate the diagnostic value of a new photodynamic diagnosis (PDD) system using 5-aminolevulinic acid (ALA) for the diagnosis of bladder tumors. To validate whether false-positive findings caused by tangent effects in PDD can be resolved, we compared diagnostic accuracies between the new PDD system and a conventional PDD system. PATIENTS AND METHODS: Among 30 transurethral bladder biopsies, 15 cases received ALA-PDD using rigid fluorescence cystoscopy (conventional PDD system), and flexible fluorescence cystoscopy with a twin mode monitor (new PDD system) was used in a separate set of 15 cases. To evaluated the usefulness of ALA-PDD, diagnostic accuracies were retrospectively compared between the conventional PDD system and the new PDD system. RESULTS: Of 207 specimens from 30 cases, we obtained 110 specimens using the conventional PDD system and 97 specimens using the new PDD system. Of these samples, we selected 30 distal bladder specimens each from both the conventional PDD system and the new PDD system. The overall sensitivity, specificity and false-positive rate for the new PDD system were 100%, 82.6%, and 17.4%, respectively. Those of the conventional PDD system were 83.3%, 66.2% and 33.8%, respectively. The overall false-positive rate of the new PDD system improved to 16.4% when compared with the conventional PDD system. Furthermore, the false-positive rate of the new PDD system in distal bladder samples improved to 11.8%. The overall AUC of the new PDD system was significantly greater compared with that of the conventional PDD system (P<0.05). We obtained similar significant results in the distal bladder samples (P<0.05). All procedures were well tolerated by all patients without any severe adverse events. CONCLUSION: Flexible cystoscopy had a significantly higher specificity and improved incidence of tangent effects when compared with conventional methods. This preliminary study suggests that the new PDD system using 5-aminolevulinic acid may be more useful than the conventional PDD system.	bladder
Lymph node count at radical cystectomy does not influence long-term survival if surgeons adhere to a standardized template.	INTRODUCTION: Multiple bladder cancer studies report that the number of removed lymph nodes (lymph node count [LNC]) at radical cystectomy (RC) is positively associated with survival. Although these reports suggest that LNC can be used as a proxy for surgical quality, all studies used variable or inconsistent pelvic lymph node dissection (PLND) templates. We therefore wished to establish whether LNC at RC influences survival if surgeons adhere to a standardized PLND template. MATERIALS AND METHODS: We included 274 patients who underwent RC from January 2005 until December 2012. All RCs were performed in either one of 2 hospitals (hospital A or B) by the same 4 urologists (all from hospital A) and a standardized PLND template was applied. PLND specimens were processed by 2 independent pathology departments (hospital A and B). We used Cox regression analysis to investigate the prognostic value of LNC adjusted for patient characteristics. We also compared LNC between hospitals and surgeons and investigated the effect of both the variables on overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). RESULTS: Median LNC was 17 (interquartile range = 12). At a median follow-up of 64.3 months, there was no association between LNC and OS (P = 0.328), CSS (P = 0.645), or DFS (P = 0.450). Median LNC was higher in hospital B than in hospital A (20.0 vs. 16.0, P = 0.003). Median LNC varied significantly among surgeons (12-20, P<0.001). Neither the hospital of surgery nor the surgeon performing PLND influenced OS (P = 0.771 and P = 0.982, respectively), CSS (P = 0.310 and P = 0.691, respectively), or DFS (P = 0.256 and P = 0.296, respectively). CONCLUSION: If surgeons adhere to a standardized template, LNC at RC does not affect long-term survival.	bladder
Disease map-based biomarker selection and pre-validation for bladder cancer diagnostic.	CONTEXT: Urinary biomarkers are promising as simple alternatives to cystoscopy for the diagnosis of de novo and recurrent bladder cancer. OBJECTIVE: To identify a highly sensitive and specific biomarker candidate set with potential clinical utility in bladder cancer. MATERIALS AND METHODS: Urinary biomarker concentrations were determined by ELISA. The performance of individual markers and marker combinations was assessed using ROC analysis. RESULTS: A five-biomarker panel (IL8, MMP9, VEGFA, PTGS2 and EN2) was defined from the candidate set. DISCUSSION AND CONCLUSION: This panel showed a better overall performance than the best individual marker. Further validation studies are needed to evaluate its clinical utility in bladder cancer.	bladder
Identification of circulating microRNA signatures for upper tract urothelial carcinoma detection.	The involvement of circulating microRNAs (miRNAs) in cancer and their potential as diagnostic and prognostic biomarkers are becoming increasingly known. However, the significance of circulating miRNAs in upper tract urothelial carcinoma (UTUC) has remained to be investigated. The present study performed a genome‑wide serum miRNA analysis using a deep sequencing platform for initial screening. Subsequently, serum samples of 46 UTUC patients and 30 cancer‑free individuals with hematuria were subjected to a quantitative reverse‑transcription polymerase chain reaction analysis. The expression of thirteen miRNAs (miR‑664a‑3p, miR‑423‑5p, miR‑431‑5p, miR‑191‑5p, miR‑92a‑3p, miR‑22‑3p, miR‑26a‑5p, miR‑33b‑3p, miR‑16‑5p, let‑7a‑5p, let‑7b‑5p, let‑7f‑5p and let‑7c) was significantly different in serum from UTUC patients compared with that in control samples. Receiver operator characteristic analysis showed that 10 miRNAs (miR‑664a‑3p, miR‑431‑5p, miR‑423‑5p, miR‑191‑5p, miR‑33b‑3p, miR‑26a‑5p, miR‑22‑3p, miR‑16‑5p, let‑7b‑5p and let‑7c) had the potential to distinguish individuals with UTUC from the controls (areas under the curve >0.8). The present study provided the first evidence for the potential use of circulating miRNAs as biomarkers for UTUC diagnosis, which remains to be verified by further studies.	bladder
Sequential gemcitabine and tamoxifen treatment enhances apoptosis and blocks transformation in bladder cancer cells.	Bladder cancer is a common malignancy for which regional or metastatic disease is identified at diagnosis. The aim of this study was to determine whether tamoxifen (Tam), an estrogen receptor (ER) antagonist, can sensitize bladder cancer cell lines to gemcitabine (Gem) chemotherapy. ERα and ERβ protein levels were determined in each cell line using western blot analysis. The TCC-Sup, 5637, and RT4 bladder cancer cells were exposed to various concentrations and regimens of Tam or Gem alone or in combination. Cell viability and apoptosis were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and propidium iodide followed by flow cytometry. Apoptosis was then evaluated by western blot analysis. Treated TCC-Sup cells were subjected to soft agar colony formation assay to determine the cellular transformation. Western blot analysis results revealed ER expression in the three cell lines. TCC-Sup and 5637 cells treated with a combination of Tam and Gem had lower cell viabilities than those treated with Tam or Gem alone for 72 h in TCC-Sup and 5637. Compared with the other treatments, sequential Gem followed by Tam (Gem→Tam) treatment caused the largest increase in DNA fragmentation at 72 h in TCC-Sup cells. Western blot analysis results revealed that this sequential Gem→Tam treatment increased poly(ADP-ribose) polymerase cleavage in TCC-Sup cells. Sequential Gem→Tam inhibited the cell transformation in TCC-Sup cells. In conclusion, sequential Gem→Tam enhanced the cytotoxicity of Gem in vitro. This regimen be useful to enhance the efficacy of Gem in bladder cancer. However, future in vivo studies are required to verify the results.	bladder
CDK4/6 Inhibition Controls Proliferation of Bladder Cancer and Transcription of RB1.	PURPOSE: The retinoblastoma signaling network is frequently altered in advanced bladder cancer. We investigated the potential of CDK4/6 as a therapeutic target and determined biomarkers for patient stratification. MATERIALS AND METHODS: Genetic alterations were analyzed using public databases, including TCGA (The Cancer Genome Atlas), COSMIC (Catalogue of Somatic Mutations in Cancer) and CCLE (Cancer Cell Line Encyclopedia). Effects of the CDK4/6-inhibitor PD-0332991 or LY2835219 were examined in 10 bladder cancer cell lines by immunoblot, cell viability, apoptosis and cell cycle progression. Efficacy of the PD-0332991 and cisplatin combination was analyzed using the combination index. Gene expression level was determined by quantitative polymerase chain reaction. Cytomegalovirus promoter regulated recombinant retinoblastoma was used for reconstitution. Three-dimensional xenografts were grown on chicken chorioallantoic membrane and analyzed by measuring tumor weight and immunohistochemical expression of total retinoblastoma and Ki-67. RESULTS: PD-0332991 treatment decreased the proliferation of retinoblastoma positive bladder cancer cell lines and was synergistic in combination with cisplatin. PD-0332991 or LY2835219 treatment decreased the phosphorylation, total protein and transcript level of retinoblastoma. Treatment resulted in a decrease in E2F target gene expression (CCNA2 and CCNE2) and cell cycle progression from G0/G1 to the S-phase but did not affect apoptosis. In retinoblastoma negative cells reconstituted with recombinant retinoblastoma PD-0332991 affected only phosphorylation and not the total retinoblastoma level. These cells remained resistant to treatment. In 3-dimensional retinoblastoma xenografts, treatment resulted in reduced tumor weight and decreased expression of total retinoblastoma and Ki-67. CONCLUSIONS: We provide preclinical evidence that CDK4/6 inhibition is a potential therapeutic strategy for retinoblastoma positive bladder cancer that probably acts by negatively regulating retinoblastoma transcription.	bladder
Double-negative feedback loop between long non-coding RNA TUG1 and miR-145 promotes epithelial to mesenchymal transition and radioresistance in human bladder cancer cells.	LncRNAs have a critical role in the regulation of cellular processes such as cancer progression and metastasis. In the present study, we confirmed that TUG1 was overexpressed in bladder cancer tissues and established cell lines. Knockdown of TUG1 inhibited bladder cancer cell metastasis both in vitro and in vivo. Furthermore, we found that TUG1 promoted cancer cell invasion and radioresistance through inducing epithelial-to-mesenchymal transition (EMT). Interestingly, TUG1 decreased the expression of miR-145 and there was a reciprocal repression between TUG1 and miR-145 in an Argonaute2-dependent manner. ZEB2 was identified as a down-stream target of miR-145 and TUG1 exerted its function through the miR-145/ZEB2 axis. In summary, our data indicated that blocking TUG1 function may be an effective anti-cancer therapy.	bladder
Evaluating Evidence for Association of Human Bladder Cancer with Drinking-Water Chlorination Disinfection By-Products.	Exposure to chlorination disinfection by-products (CxDBPs) is prevalent in populations using chlorination-based methods to disinfect public water supplies. Multifaceted research has been directed for decades to identify, characterize, and understand the toxicology of these compounds, control and minimize their formation, and conduct epidemiologic studies related to exposure. Urinary bladder cancer has been the health risk most consistently associated with CxDBPs in epidemiologic studies. An international workshop was held to (1) discuss the qualitative strengths and limitations that inform the association between bladder cancer and CxDBPs in the context of possible causation, (2) identify knowledge gaps for this topic in relation to chlorine/chloramine-based disinfection practice(s) in the United States, and (3) assess the evidence for informing risk management. Epidemiological evidence linking exposures to CxDBPs in drinking water to human bladder cancer risk provides insight into causality. However, because of imprecise, inaccurate, or incomplete estimation of CxDBPs levels in epidemiologic studies, translation from hazard identification directly to risk management and regulatory policy for CxDBPs can be challenging. Quantitative risk estimates derived from toxicological risk assessment for CxDBPs currently cannot be reconciled with those from epidemiologic studies, notwithstanding the complexities involved, making regulatory interpretation difficult. Evidence presented here has both strengths and limitations that require additional studies to resolve and improve the understanding of exposure response relationships. Replication of epidemiologic findings in independent populations with further elaboration of exposure assessment is needed to strengthen the knowledge base needed to better inform effective regulatory approaches.	bladder
Randomized Controlled Study of the Efficacy, Safety and Quality of Life with Low Dose bacillus Calmette-Guérin Instillation Therapy for Nonmuscle Invasive Bladder Cancer.	PURPOSE: The optimal dose of intravesical bacillus Calmette-Guérin for the treatment of nonmuscle invasive bladder cancer is controversial. We investigated if induction therapy with low dose bacillus Calmette-Guérin could achieve a complete response rate similar to that of standard dose bacillus Calmette-Guérin, with less toxicity and higher quality of life. MATERIALS AND METHODS: After transurethral resection, patients with unresectable multiple nonmuscle invasive bladder cancer and/or carcinoma in situ were randomized to receive standard (80 mg) or low dose (40 mg) bacillus Calmette-Guérin instillation induction therapy (weekly, 8 times). The primary end point was noninferiority of low dose bacillus Calmette-Guérin with a null hypothesis of a 15% decrease in complete response rate. Secondary end points were recurrence-free survival, progression-free survival, overall survival, patient compliance, adverse events and quality of life using the EORTC QLQ-C30. RESULTS: In an intent to treat analysis of 166 patients the complete response rates for low dose and standard dose bacillus Calmette-Guérin were 79% (95% CI 0.70-0.88) and 85% (95% CI 0.77-0.92), respectively. Dunnett-Gent analysis revealed that the null hypothesis of inferiority of low dose bacillus Calmette-Guérin in terms of complete response could not be rejected (p = 0.119). However, there were no significant differences between the groups in terms of recurrence, progression and overall survival. Low dose bacillus Calmette-Guérin was associated with significantly less fever (p = 0.001) and micturition pain (p = 0.047), and significantly higher quality of life scores for global quality of life, role functioning and functional impairment. CONCLUSIONS: The noninferiority of low dose bacillus Calmette-Guérin was not proven. However, low dose bacillus Calmette-Guérin was associated with lower toxicity and higher quality of life compared to standard dose bacillus Calmette-Guérin in patients with nonmuscle invasive bladder cancer.	bladder